Related Experiment Video

Updated: Oct 21, 2025

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
11:28

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Published on: October 7, 2011

11.2K

High-Order Epistasis and Functional Coupling of Infection Steps Drive Virus Evolution toward Independence from a Host

Minetaro Arita1

  • 1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

Microbiology Spectrum
|September 1, 2021
PubMed

Insights

Poliovirus evolved to replicate independently of host factors PI4KB and OSBP through four specific mutations. The mutations 3A-R54W and 2B-F17L are essential, with 2B-Q20H enabling efficient viral spread and replication.

Area of Science:

  • Virology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The phosphatidylinositol-4 kinase IIIβ (PI4KB)/oxysterol-binding protein (OSBP) pathway is crucial for poliovirus (PV) replication.
  • Poliovirus typically relies on this host pathway for viral plus-strand RNA synthesis.

Purpose of the Study:

  • To investigate how poliovirus evolves to become independent of the PI4KB/OSBP host pathway.
  • To elucidate the roles of specific mutations in viral adaptation and replication.

Main Methods:

  • Experimental evolution of poliovirus in vitro.
  • Quantitative analysis of viral infection steps, including replication, growth, and spread.
  • Analysis of recessive epistasis between viral mutations.

Main Results:

  • Four mutations enable poliovirus to achieve substantial independence from the PI4KB/OSBP pathway.
  • Mutations 3A-R54W and 2B-F17L are essential for replication via recessive epistasis.
  • Mutation 2B-Q20H, dependent on the prior mutations, enhances viral replication, growth, and spread.
  • Increased plus-strand to minus-strand RNA ratio observed in PI4KB/OSBP-independent infections.

Conclusions:

  • Viral evolution can lead to independence from essential host pathways through multi-tiered epistasis.
  • Functional coupling of infection steps is critical for the efficacy of adaptive mutations.
  • This study provides insights into the evolutionary mechanisms enabling viruses to overcome reliance on host factors.
Keywords:
OSBPPI4KBenterovirusepistasisevolutionevolutionary biologyresistancevirusvirus-host interactions

More Related Videos

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors06:02

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors

Published on: September 13, 2018

7.0K
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

10.7K

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
35.4K
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
265
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
13.1K
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
24.0K
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
47.7K
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
251